The present invention, in some embodiments thereof, relates to a method and apparatus for the detection, diagnosis and monitoring of osteoporosis and, more particularly, but not exclusively, to such a method and apparatus that does not require ionizing radiation.
Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture. It is widely acknowledged that bone strength and resistance to fracture depend, not only on the Bone Mineral Density (BMD), but also on the bone quality—its architecture, turnover rate, micro-fractures and degree of mineralization. The disease is extremely widespread: more than 1 in 3 women and 1 in 5 men will sustain at least one osteoporotic fracture in their lifetimes. By comparison, a woman's risk of breaking a hip due to osteoporosis is equal to her risk of breast, ovarian and uterine cancer combined, a man at age 50 or older is more likely to break a bone due to osteoporosis than he is to get prostate cancer. The consequences of fractures are fearsome—50% of all patients suffering from a hip fracture will never walk again and 20% of all patients suffering from a hip fracture will die within one year.
The disease is considered a major public health problem worldwide due to the number of fractures and the related overwhelming healthcare costs—tens of billions of dollars annually. By comparison, the healthcare costs of all osteoporosis-related fractures is currently equivalent to the healthcare costs of all cardiovascular disease and asthma combined. The vast majority of patients are not diagnosed until the osteoporosis is fully developed and fracture occurs that requires long term treatments. Identifying and treating patients at risk of fracture, but who have not yet sustained a fracture, can substantially reduce the five-year fracture incidence and related healthcare costs accordingly.
Currently, the Dual-energy X-ray Absorptiometry (DXA) method, which measures the BMD, is the gold standard measurement and the clinically accepted screening tool. However, DXA is inefficient for detecting bone loss at women younger than 60, it is costly many tens of USD per test) and involves ionizing radiation which causes patient non-compliance with the test. Since DXA measures only BMD and not bone quality, it can only predict the risk of 70% of all osteoporotic fractures and only for the elderly population where osteoporosis has fully developed. Bone loss may actually begin at the age of 30 but it is too small to be detected by DXA and it is extremely difficult to revert after osteoporosis has developed.
Thus, there is a need for non-invasive, non-ionizing and cost-effective screening tool to detect the disease as early as possible based on its pathological expressions and to monitoring disease progression during treatment.
An attempt to address some of the drawbacks of DXA is made using ultrasonic methods. Quantitative Ultrasound (QUS) represents an umbrella of techniques that attempt to characterize the biomechanical strength of bones by measuring the parameters of ultrasound transmitted through the bone in-vivo 11. Most QUS techniques measure some variants of Broadband Ultrasonic Attenuation (BUA) or the Speed of Sound (SOS) of the ultrasonic pulse propagating through the bone. These parameters correspond to the amplitude and phase of the ultrasonic transfer function of the bone.
Theoretical models have shown that these parameters are affected by both bone density and microstructure and thus, at least on theoretical grounds, provide a better estimate of the risk of fracture. However, clinical use QUS has yet to demonstrate superiority over DXA or to show statistically significant successes in assessing the bone functional status. The reason for this might be the inherent insensitivity of ultrasound to molecular and functional changes in the tissue.
In contrast, optical methods are uniquely qualified for probing tissue functional status due to their inherent noninvasiveness and the highly informative content encoded in the spectral signatures of tissue constituents.
Attenburrow et al.—cited as Ugryumova, N., Matcher, S. J. & Attenburrow, D. P. Measurement of bone mineral density via light scattering, Physics in medicine and biology 49, 469 (2004)—have shown in-vitro that bone demineralization, such as present in osteoporosis, causes great changes in the absorption and scattering properties of the bone. Pifferi, A. et al. Optical biopsy of bone tissue: a step toward the diagnosis of bone pathologies. Journal of Biomedical Optics 9, 474 (2004) have shown in-vivo that the near Infrared (NIR) optical absorption and transmission through the calcaneus bone are dependent on the age of the subject and are related to the state of the bone. However, pure optical methods which rely upon scattered photons which escape the tissue through transmission or back reflection are limited in their imaging depth or resolution due to their reliance on very weak signals. This is especially true in bone tissue where the overwhelming scattering (μs_150 cm−1 at NIR wavelengths 18) greatly restricts the number of photons reaching the detector.
Photoacoustic (PA) imaging is renowned for its ability to produce high resolution in-vivo images at depths where none of the other optical bio-imaging techniques can. PA signals carries information about the molecular content and functional state at the absorption sites due to the direct dependence of PA signal generation on the absorption properties of the medium.
When a short laser pulse irradiates an absorbing medium there is local absorption, which leads to local heating and local expansion. This local expansion leads to ultrasonic pressure waves that travel through the medium at the speed of sound, and can be recorded using high frequency pressure sensors. The slow speed of sound in tissue (˜1500 m/s) in comparison to the speed of light allows for the time resolved detection of these pressure waves and the determination of depth from where these pressure waves originated. By using an array of sensors the temporal delay of the incoming pressure wave fronts can be combined into an ultrasound image.
Although the technology is still in its infancy, photoacoustic imaging is being employed in the development of various devices. Such devices include breast cancer detection equipment, as well as equipment used for measuring oxygenation levels. In both cases, the change in the optical properties of blood in respect to oxygen saturation and the strong optical contrast between hemoglobin and surrounding tissue is utilized. Recently, Zhao et al. have demonstrated single wavelength photoacoustic excitation and detection on bone samples coated with Gelatin. They used low frequency ultrasound of 50 kHz to investigate the slow Fundamental Flexural Guided Wave.